Combination of Pembrolizumab with Electrochemotherapy in Cutaneous Metastases from Melanoma: A Comparative Retrospective Study from the InspECT and Slovenian Cancer Registry

Electrochemotherapy (ECT) is an effective locoregional therapy for cutaneous melanoma metastases and has been safely combined with immune checkpoint inhibitors in preliminary experiences. Since ECT is known to induce immunogenic cell death, its combination with immune checkpoint inhibitors might be beneficial. In this study, we aimed to investigate the effectiveness of ECT on cutaneous melanoma metastases in combination with pembrolizumab. We undertook a retrospective matched cohort analysis of stage IIIC–IV melanoma patients, included in the International Network for sharing practices of ECT (InspECT) and the Slovenian Cancer Registry. We compared the outcome of patients who received the following treatments: (a) pembrolizumab alone, (b) pembrolizumab plus ECT, and (c) ECT. The groups were matched for age, sex, performance status, and size of skin metastases. The local objective response rate (ORR) was higher in the pembrolizumab-ECT group than in the pembrolizumab group (78% and 39%, p < 0.001). The 1 year local progression-free survival (LPFS) rates were 86% and 51% (p < 0.001), and the 1 year systemic PFS rates were 64% and 39%, respectively (p = 0.034). The 1 year overall survival (OS) rates were 88% and 64%, respectively (p = 0.006). Our results suggest that skin-directed therapy with ECT improves superficial tumor control in melanoma patients treated with pembrolizumab. Interestingly, we observed longer PFS and OS in the pembrolizumab-ECT group than in the pembrolizumab group. These findings warrant prospective confirmation.

Download Full-text

Volume increase of spleen in melanoma patients undergoing immune checkpoint blockade

Immunotherapy ◽

10.2217/imt-2021-0022 ◽

2021 ◽

Author(s):

Laura Susok ◽

Dominik Reinert ◽

Carsten Lukas ◽

Eggert Stockfleth ◽

Thilo Gambichler

Keyword(s):

Immune Checkpoint ◽

Cutaneous Melanoma ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Immune Checkpoint Blockade ◽

Clinical Parameters ◽

Spleen Volume ◽

Volume Increase ◽

Computer Tomographic ◽

Melanoma Patients

Aim: To find out whether treatment with immune checkpoint inhibitors (ICIs) results in volume increase of the spleen. Patient & methods: We studied 49 stage III and IV melanoma patients with an indication for ICIs. Computer tomographic-assisted volumetry of spleens was performed. Results: After 3 months, median spleen volume was significantly increased when compared with the baseline volume. At 3 months, the increase of spleen volume was significantly associated with the use of ipilimumab and ipilimumab plus nivolumab. There was no significant association between spleen volume increase and clinical parameters. Conclusion: The median spleen volume of patients with cutaneous melanoma increases during the first months of ICI treatment, which was particularly attributable to the use of anti-CTLA-4 and anti-CTLA-4/anti-PD-1 regimens.

Download Full-text

Immune Profile Of Uveal Melanoma Patients: Impact On Clinical Outcome

10.21203/rs.3.rs-614744/v1 ◽

2021 ◽

Author(s):

Ernesto Rossi ◽

Ilaria Grazia Zizzari ◽

Alessandra Di Filippo ◽

Anna Acampora ◽

Monica Maria Pagliara ◽

...

Keyword(s):

Uveal Melanoma ◽

Immune Checkpoint ◽

Cutaneous Melanoma ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Therapeutic Option ◽

Immune Profile ◽

Melanoma Patients ◽

Low Activity

Abstract Background. Immunotherapy represents a common therapeutic option for metastatic uveal melanoma, despite the low activity. Although overall survival is often dismal, long survivors can be observed. In this study, the prognostic role of the soluble isoforms of immunomodulatory receptors and cytokines/chemokines was evaluated as well as their ability to identify patients who can benefit more from anti-PD-1 therapy. Methods. Sera from 22 metastatic uveal melanoma patients were assayed to evaluate the levels of cytokines/chemokines and soluble immune checkpoint molecules by multiplex immunoassay analysis. The changes of these molecules during anti-PD-1 therapy were assessed. The correlation between soluble isoforms of immunomodulatory receptors/cytokines/chemokines and survival was analysed. A comparison between circulating immune profile of metastatic uveal melanoma and cutaneous melanoma during anti-PD-1 therapy was also performed. Results. The levels of sCD137, sCD28, sPD-1, sPD-L2 sLAG3, sCD80 and sTim3 were significantly enhanced during anti-PD-1 treatment. Similarly, the levels of IP-10, CCL2 and IDO activity were significantly increased during anti-PD-1 therapy. HVEM, IL-8 and IDO activity were higher in patients with survival < 6 months. Considering these 3 molecules, we obtained a score able to predict patients’ survival. Serum CD137, sGITR and sCD27 were significantly lower in patients with survival > 30 months. Serum GITR, sCD27, sPD-1, sCD80, IFNγ and IDO activity were significantly higher in uveal melanoma patients than in cutaneous melanoma patients during anti-PD-1 therapy. Conclusions. The molecules detected in uveal melanoma during anti-PD-1 treatment reflect the poor activation of immune system and may justify the limited response to immune checkpoint inhibitors. Nevertheless, some patients with metastatic uveal melanoma had a long survival. These patients could be identified through a score based on circulating immune molecules such as HVEM, IDO and IL-8. The comparison of immune profile during anti-PD-1 therapy between uveal melanoma and cutaneous melanoma reflects the different efficacy of immune checkpoint inhibitors in these diseases.

Download Full-text

Expression of IL4 Induced Gene 1 in Patients With Cutaneous Melanoma: Value in Prognosis and/or in Predictive Response to Immune Checkpoint Inhibitors

Case Medical Research ◽

10.31525/ct1-nct04253080 ◽

2020 ◽

Author(s):

Keyword(s):

Immune Checkpoint ◽

Cutaneous Melanoma ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Predictive Response

Download Full-text

Vitiligo induced by immune checkpoint inhibitors in melanoma patients: an expert opinion

Expert Opinion on Drug Safety ◽

10.1080/14740338.2021.1915279 ◽

2021 ◽

pp. 1-6

Author(s):

Janny E. Lommerts ◽

Marcel W. Bekkenk ◽

Rosalie M. Luiten

Keyword(s):

Expert Opinion ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Melanoma Patients

Download Full-text

Evaluation of the modified immune prognostic index to prognosticate outcomes in metastatic uveal melanoma patients treated with immune checkpoint inhibitors

Cancer Medicine ◽

10.1002/cam4.3784 ◽

2021 ◽

Vol 10 (8) ◽

pp. 2618-2626

Author(s):

Michael S. Sander ◽

Igor Stukalin ◽

Isabelle A. Vallerand ◽

Siddhartha Goutam ◽

Benjamin W. Ewanchuk ◽

...

Keyword(s):

Uveal Melanoma ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Prognostic Index ◽

Melanoma Patients

Download Full-text

The Efficacy of Anti-PD-L1 Treatment in Melanoma Is Associated with the Expression of the ECM Molecule EMILIN2

International Journal of Molecular Sciences ◽

10.3390/ijms22147511 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7511

Author(s):

Albina Fejza ◽

Maurizio Polano ◽

Lucrezia Camicia ◽

Evelina Poletto ◽

Greta Carobolante ◽

...

Keyword(s):

Gene Expression ◽

Effective Treatment ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Tumor Hypoxia ◽

Melanoma Cells ◽

Vessel Normalization ◽

Melanoma Patients

The use of immune checkpoint inhibitors has revolutionized the treatment of melanoma patients, leading to remarkable improvements in the cure. However, to ensure a safe and effective treatment, there is the need to develop markers to identify the patients that would most likely respond to the therapies. The microenvironment is gaining attention in this context, since it can regulate both the immunotherapy efficacyand angiogenesis, which is known to be affected by treatment. Here, we investigated the putative role of the ECM molecule EMILIN-2, a tumor suppressive and pro-angiogenic molecule. We verified that the EMILIN2 expression is variable among melanoma patients and is associated with the response to PD-L1 inhibitors. Consistently, in preclinical settings,the absence of EMILIN-2 is associated with higher PD-L1 expression and increased immunotherapy efficacy. We verified that EMILIN-2 modulates PD-L1 expression in melanoma cells through indirect immune-dependent mechanisms. Notably, upon PD-L1 blockage, Emilin2−/− mice displayed improved intra-tumoral vessel normalization and decreased tumor hypoxia. Finally, we provide evidence indicating that the inclusion of EMILIN2 in a number of gene expression signatures improves their predictive potential, a further indication that the analysis of this molecule may be key for the development of new markers to predict immunotherapy efficacy.

Download Full-text